Respiratory Syncytial Virus


Human respiratory syncytial virus (HRSV) is a ubiquitous ribonucleic acid (RNA) virus that represents the leading cause of acute lower respiratory infections (mainly bronchiolitis and pneumonia) in infants and young children worldwide. HRSV belongs to the Pneumovirinae subfamily within the Paramyxoviridae family of enveloped, negative‐strand RNA viruses. Epithelial cells lining the nasal passages and respiratory tract are the primary target of HRSV infection, although alveolar macrophages and dendritic cells are also infected. Infected cells respond by producing a variety of cytokines, chemokines and interferons that are involved in the inflammatory response to HRSV. Although primary HRSV infection occurs at an early age, immunity is short‐lived or incomplete and re‐infections occur throughout life. Initial efforts to develop a vaccine based on formalin‐inactivated HRSV resulted in vaccine‐enhanced disease, and there is still no licensed prophylactic HRSV vaccine available.

Key Concepts:

  • Human respiratory syncytial virus (HRSV) is the leading cause of serious respiratory tract disease in children and infants worldwide.

  • HRSV belongs to the Pneumovirinae subfamily within the Paramyxoviridae family of negative‐strand RNA viruses.

  • The HRSV genome comprises 10 genes that encode 11 viral proteins.

  • HRSV derives its name from the formation of multinucleated, fused cells (syncytia), which are the hallmark of infection of cultured cells or lung tissue.

  • Following attachment to the target cell, entry by HRSV is mediated by fusion of the viral envelope with the host cell plasma membrane at neutral pH.

  • The entire replication cycle of HRSV takes place in the cytoplasm of the infected cell.

  • Reverse genetics has permitted the recovery of infectious HRSV from complementary DNA.

  • HRSV strains disseminate rapidly worldwide, accumulating mutations predominantly in the attachment protein, probably as a consequence of immune selection.

  • Pathology associated with HRSV infections is not only the result of direct virus injury, but largely the consequence of an aberrant immune/inflammatory response.

  • Palivizumab, a neutralising monoclonal antibody directed against HRSV fusion protein, is the only product available on the market for prophylactic treatment of children at high risk of severe infection.

Keywords: negative‐strand RNA viruses; subfamily Pneumovirinae; bronchiolitis; membrane fusion; pathogenesis; vaccines; antivirals

Figure 1.

Paramyxovirus genome organisation. Gene maps for representative members of each genus of the Paramyxovirinae and Pneumovirinae subfamilies are shown. The nucleotide length of each viral genome (nt), the intergenic regions and the noncoding termini (not to scale) are shown. Genes are colour‐coded for function and the overlap between the HRSV M2 and L genes is indicated.

Figure 2.

Human respiratory syncytial virus structure. (a) Negative‐stained preparation of partially‐purified HRSV (A2 strain). Electron micrograph by Lesley Calder, National Institute for Medical Research, London, UK, reproduced at a magnification of 90 000×. (b) Schematic diagram of the HRSV virion (not to scale). The colour coding of proteins matches that of Figure . Virion diagram provided by Alfonsina Trento, ISCIII, Madrid, Spain.

Figure 3.

Human respiratory syncytial virus G glycoprotein. The full length, 298 amino acid membrane‐anchored G protein (Gm) and the 233 amino acid soluble G protein (Gs) are shown (Long strain). Gs is formed by alternative translation initiation at M48, followed by cleavage after residue 65. Inverted triangles represent N‐glycosylation sites and vertical lines indicate O‐linked glycosylation sites. Cysteine residues overlapping the central conserved domain are represented by solid circles. The lower part of the figure depicts a model of the 3‐dimensional structure of Gm. Although Gm is probably tetrameric, a dimer is shown for simplicity. Antibody epitopes and the glycosaminoglycan (GAG)‐binding site are indicated by arrows. Adapted from Melero with permission from Elsevier. Figure provided by Alfonsina Trento, ISCIII, Madrid, Spain.

Figure 4.

Human respiratory syncytial virus fusion (F) glycoprotein. (a) Hydrophobic signal peptide (SP), fusion peptide (FP) and transmembrane (TM) regions are shown as hatched boxes. The arrows indicate the double cleavage sites of F0 that yield disulphide‐linked (S–S) F2 (black) and F1 (red) chains. Heptad repeat sequences HRA and HRB are shown in green and blue, respectively. Also indicated are the locations of the F protein antigenic sites. Three‐dimensional models of the trimeric prefusion (b) and postfusion (c) structures are shown, with cleavage sites indicated by arrows. The backbone is coloured grey and a single monomer is colored to the same scheme as in part (a). Models were built using the SWISS‐MODEL server facilities ( and the atomic coordinates of the prefusion structure of the parainfluenza virus 5 F protein (Protein Data Bank code, 2B9B) or the postfusion structure of the parainfluenza virus 3 F protein (Protein Data Bank code, 1ZTM) as templates (Yin et al., ). Figure provided by Margarita Magro, ISCIII, Madrid, Spain.

Figure 5.

Global distribution of viruses belonging to the BA genotype with a 60 nucleotide duplication in the G protein gene. Different lineages are colour coded and for each lineage the years of circulation are shown on the right. Reproduced from Trento et al. with permission from the American Society for Microbiology. Figure provided by Alfonsina Trento.



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Further Reading

Collins PL and Crowe JE (2007) Respiratory syncytial virus and metapneumovirus. In: Knipe DM, Howley PM, Griffin DE et al. (eds) Fields Virology, 5th edn, pp. 1601–1646. Philadelphia, PA: Lippincott‐Raven.

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Lamb RA and Jardetzky TS (2007) Structural basis of virus invasion: lessons from paramyxovirus F. Current Opinion in Structural Biology 17: 427–436.

Nokes JD and Cane PA (2008) New strategies for control of respiratory syncytial virus infection. Current Opinion in Infectious Disease 21: 639–643.

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Rawling, Joanna, and Melero, José A(Apr 2011) Respiratory Syncytial Virus. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000429.pub3]